Drugs in use today for the treatment of mental disorders most often are associated with serious side effects. Antipsychotic drugs commonly cause disturbing extrapyramidal symptoms, and long term treatment may result in tardive dyskinesia. Antidepressants often exhibit cardiotoxicity, and anxiolytic drugs have addicting properties. As a result of these drawbacks efforts are being made to fine new pharmacologically active drugs which have fewer side effects.
The present invention relates to novel piperazine- and homopiperazinecarboxamides bearing a phenoxyalkyl or thiophenoxyalkyl side chain, which exhibit valuable pharmacological properties, and which have a low tendency to cause side effects.
Pharmacologically valuable piperazine carboxamides are previously known from British patent application No. 2,037,745. However, the compounds according to the British application differ from the compounds according to the present invention in being substituted in the 4-position with a very lipophilic 4,4-diphenylbutyl group. Furthermore, these previous compounds are very active in pharmacological models which may indicate potentation of noradrenaline and serotonine (e.g inhibition of muricide behaviour), which in turn may cause unwanted side effects, e.g. aneroxigenic. The compounds of the present invention are considerably less active in these pharmacological models indicating that fewer side effects are to be expected when compounds according to the present invention are used.
Piperazinecarboxamides substituted the 4-position with a butyrophenone side chain are known from Collect. Czech. Chem. Commun 1975, 40(4), 1218-30. The butyrophenone side chain is chemically distinctly different from a phenoxyalkyl or thiophenoxyalkyl group. Besides, the authors state that their compounds display CNS-activity only at high doses.
The French patent application 2367067 and the Swedish patent application 8100852-6 describe piperazine derivatives having a phenoxyalkyl side chain but in neither case are the compounds piperazinecarboxamides. The compounds according to the French patent application are chracterized by an analgesic effect that is not accompanied by any secondary effects (cf. the French application page 1, lines 20-24).